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  • Cited by 1
  • Print publication year: 2002
  • Online publication date: November 2009

3 - Peroxynitrite and injury to the vasculature and central nervous system in stroke and neurodegeneration

from Part II - Oxidative stress
    • By Joseph S. Beckman, Departments of Anesthesiology, Biochemistry, and Neurobiology, University of Alabama at Birmingham, Birmingham, AL, John Crow, Departments of Anesthesiology and Pharmacology, University of Alabama at Birmingham, Birmingham, AL, Alvaro G. Estévez, Departments of Pharmacology and Physiology, University of Alabama at Birmingham, Birmingham, AL
  • Edited by Pak H. Chan, Stanford University, California
  • Publisher: Cambridge University Press
  • DOI: https://doi.org/10.1017/CBO9780511544910.004
  • pp 23-46

Summary

Introduction

Oxidative stress is a widely recognized but poorly understood component in stroke and neurodegeneration. Antioxidant enzymes as well as a variety of low molecular weight antioxidants can be remarkably protective in animal models in stroke, trauma and neurodegenerative diseases. However, the targets and even the nature of the reactive species themselves have so far been poorly delineated. The extraordinary reactivity of some oxidants such as the hydroxyl radical has masked the search for specific targets of oxidative damage in vivo. Growing evidence indicates that oxygen radicals can produce remarkably specific actions far upstream in signaling cascades that can initiate apoptosis in neurodegeneration. In addition, oxygen radicals exert an important role in promoting thrombosis and permeability increases in the vasculature that can greatly complicate the final outcome from stroke. In this chapter, we will review how oxidative stress resulting from the interactions of superoxide with nitric oxide could be involved in damage both to the cerebral vasculature and to neurons in stroke.

Oxygen toxicity and superoxide

A strong case can be made for molecular oxygen in the air we breathe being the most dangerous toxin and carcinogen in the environment. From a thermodynamic point of view, molecular oxygen is capable of oxidizing any biological molecule and routinely does so as the terminal electron acceptor in normal metabolism. However, the rates of such reactions occurring spontaneously with oxygen are quite slow, which allows us to exist in an atmosphere containing 20% oxygen.